In recent years it has been found that several neurodegenerative disorders are caused by protein misfolding and/or misaggregation.
One of the most important and initial step of Alzheimer's disease (AD), for instance, involves proteolytic cleavage of APP (amyloid precursor protein,) releasing short 40, 42 and 43 aa peptides (beta amyloid 1-40, 1-42, and 1-43). The degeneration of neurons is due to polymerization of beta-amyloid peptides (Ap) and subsequent neuronal deposit (amyloid). Monomeric Aβ is a product of normal metabolism and is not toxic to neuronal cells. As it forms multimeric and polymeric assemblies of itself, Aβ acquires potent toxicity for neuronal cells. Inhibition of this polymerization process has thus been identified as a potential approach to the treatment of AD and all other related pathologies where the anatomopathological hallmark is the presence of Aβ deposit.
Amyloid like-disorders might be far more widespread than previously thought, and might include many common neurodegenerative and neuromuscular pathologies, as well as prion disease. Prion diseases can be either sporadic or infectious, and until recently were not known to be associated with protein misfolding and deposition. Prions are composed solely of a misfolded prion protein (PrPSc) isoform of a glicolipid-anchored host protein. Patients with prion diseases develop progressive neurologic dysfunction. Prion diseases are invariably fatal and no effective therapy exists till now. Compounds that inhibit PrPSc formation including Congo red, are effective in scrapie-infected cultured cells.
It has also been found that the formation of intraneuronal deposits called Lewy bodies and Lewy neurites is due to aggregates of another protein, alpha-synuclein, whose misfolding and misaggregation is also believed to be one of the causes of both AD and Parkinson's disease.
U.S. Pat. No. 3,184,510 discloses N-alkoxy and N-hydroxyphenylethylamines of the following general formula:

wherein
X and Y, independently of each other, are H, OH or OCH3;
Z is H or OH;
R is H or CH3;
R′ is H, CH3, C2H5, C3H7 or i-C3H7;
R″ is CH3, C2H5, C3H7 or i-C3H7 
and their use for sustaining and/or raising blood pressure, their use as local vasoconstrictors and/or in the relaxation of the bronchial smooth muscles and of the intestinal tract, in pupil dilation and in the stimulation of adrenergic nerves. No CNS activity was disclosed.
GB 1,062,299 discloses 3,4-dihydroxyphenyl-propane derivatives of the general formula Ar—CH2—C(CH3)—NH(OR), wherein Ar is 3,4-dihydroxyphenyl and R is H or C1-C8 alkyl, as hypertensive agents.
Major, R. T. and Ohly, K. W. J. (Med. and Pharmaceut. Chem. 1961, 4, 51-65) described the synthesis of N-alkoxy-N-(2-phenyl)-isopropylamines of formula C6H5CH2CH(CH3)NHOR wherein R is CH3, C2H5 or i-C3H7, and tested the compounds for MAO inhibitory activity.
Benington, F.; Morin, R. D. and Clark, L. C. Jr. (J. Med. Chem. 1965, 8, 100-104) described the synthesis of ring-substituted 1-aryl-2-hydroxyamino- and 1-aryl-2-methoxyamino-propanes and demonstrated that the compounds were general central stimulants.
Kende et al. described in Tetrahedron Letters 1991, 14, 1699-1702 the synthesis of hydroxylamino derivatives using samarium diiodide as reducing agent.
None of the above mentioned documents mentions the use of the compounds as inhibitors of protein and/or peptide fibrils aggregation.
W099/62505 describes a method for the treatment of a neurodegenerative disorder comprising the administration of compounds able to inhibit the binding of an amyloid beta peptide to alpha-7 nicotinic acetylcholine receptors. This patent application claims compounds of the general formula:

wherein R2 is selected from hydrogen, C1-C6 alkyl, aryl or C7-C10 aralkyl and R3is selected from hydrogen, C1-C6 alkyl or C3-C10 alkenyl.
WO 01/30979 discloses pharmaceutical compositions comprising primary N-hydroxylamines of the general formula NHOHCR1R2R3, wherein R1, R2 and R3 are independently selected from hydrogen, substituted or unsubstituted (C1-C10) alkyl, alkenyl, alkynyl, aryl, acyl, carboxyl, amino, nitro, nitroso, oxime, hydrazone, azo, thiol, sulfonyl and halide and their use for reducing oxidative damage.